Biology, Neuroscience

Individuals with nonverbal learning disabilities (NLD) have an impaired ability to interpret facial expressions of emotion (FEE), the consequences of which can include progressively debilitating socioemotional disturbances. Thus, it is important to determine how the neuroanatomical structures underlying the perception of FEE in people with NLD differ from the normal population. To this end, functional magnetic resonance imaging was used to compare brain activation patterns in male and female adolescent subjects and male adult subjects with and without NLD. The subjects were presented with FEE at low and high intensities while they performed a gender decision task. Subjects with NLD displayed less activation in limbic areas responsible for processing emotion in the normal population. The NLD subjects exhibited more activity than controls in the orbital gyrus, inferior, middle and superior frontal gyri, fusiform and superior temporal gyri, insula, striatum and inferior and superior parietal lobules. Several of these structures participate in language function: as individuals with NLD have superior verbal abilities, it is probable that this population relies on their linguistic strengths to compensate for their nonverbal weaknesses whilst processing FEE. Additionally, because of an impaired capacity for attention to and discrimination of visual details, the NLD subjects showed more active responses for low intensity FEE in comparison to controls. This may have led to a failure of regions such as the middle and superior frontal and superior temporal gyri to habituate or sensitize appropriately to emotionally salient visual stimuli. In comparison with the normal population, people with NLD utilize different neural structures when processing FEE, in accordance with the strengths and deficits associated with the NLD syndrome.

This dissertation is an investigation of the sources of commonly observed event-related transients in statistical measures of interdependence: variance, cross-correlation, power spectrum density and coherence spectrum density time functions. These measures are often employed in the analysis of spatio-temporal interdependence patterns in neural activity. In order to understand the phenomenon, the origins of the variability of event-related responses are revisited. The time series of single trial cortical event-related potentials typically have a random appearance, and their trial-to-trial variability is commonly explained by the classic signal-plus-noise model, in which random ongoing background noise activity is linearly combined with a stereotyped evoked response. Here, we demonstrate that more realistic models, challenging both the linear superposition and the trial-to-trial stationarity of the event-related responses, can account for such event-related transients. In particular, two effects are considered: the nonlinear gain modulation in neural networks coupled through sigmoid functions and the trial-to-trial variability in amplitude and latency of the event phase-locked responses. An extensive analysis and characterization of both effects in interdependence measures is carried out through both analytical and numerical simulations in Chapter 2. Chapter 3 presents the outcome of testing the predicted effects on UP data recorded from implanted intracortical electrodes in monkeys performing a visuo-motor pattern discrimination task. Overall, the results point to a large contribution of the trial-to-trial variability of event phase-locked responses on the observed event-related transient in statistical interdependence measures. Because variability of the event-related responses is commonly ignored, event-related modulations in power spectral density, cross-correlation, and spectral coherence are often attributed to dynamic changes in functional connectivity within and among neural populations. It becomes then crucial the separation or removal of the trial-to-trial amplitude and latency variability effect from the statistical measures. In order to achieve this goal, the reconstruction of the single trial event phase-locked potentials is required. In Chapter 4, we approach this problem from a Bayesian inference perspective. The posterior probability density is derived for a specified number of event phase-locked components using data from single or multiple sensors. The Maximum A Posteriori solution is used to obtain the phase-locked component waveforms and their single trial parameters. The outcome is a further and definitive support for predominance of the effect of the nonstationarity of the phase-locked responses on the statistical quantities. Based on the theoretical and experimental analysis conducted in Chapters 2, 3 and 4, a framework for the statistical analysis of dynamic spatio-temporal interdependence patterns in Local Field Potential data is articulated.

The theta rhythm of the hippocampus, present in area CA1 of Ammon's horn and the dentate gyrus, is thought to serve a role in short-term memory processing. Rhythmically bursting cells of the medial septum projecting to the hippocampus are responsible for pacing theta. Further anatomical investigation of limbic-related circuitry in the rat, particularly connections of the medial septum and hippocampus, will lead to a better understanding of the pathways which influence the hippocampal EEG. Our first study examined single and collateral projections from the supramammillary nucleus to the medial septum and hippocampus, employing the retrograde fluorescent tracers FluoroGold and FluoroRuby. The supramammillary nucleus neurons we identified with collateral projections to the medial septum and hippocampus may be directly involved in generation of the theta rhythm. The second study examined single and collateral projections from the median raphe nucleus to the medial septum and hippocampus, employing the retrograde tracers FluoroGold and FluoroRuby. It has been proposed that the median raphe nucleus serves a direct role in desynchronization of the hippocampal EEG, or blockade of theta. The median raphe nucleus neurons we identified with collateral projections to the medial septum and hippocampus may be directly involved in the termination of theta, in turn modulating hippocampal memory processing. The third study examined afferent projections to the nucleus reuniens of the thalamus, employing the retrograde tracer FluoroGold, combined with a primary-antibody immunohistochemical procedure, in order to identify FluoroGold labeled cells by means of bright-field microscopy. RE afferents originate from widespread regions of the brain, providing multi-sensory and limbic input to RE. The fourth study examined efferents of the nucleus reuniens, employing the anterograde tracer PHA-L (Phaseolus vulgaris-leucoagglutinin). RE efferents terminated largely in regions of the telencephalon, and may influence working memory and sensorimotor systems. Investigations have linked the theta rhythm of the hippocampus to memory processing. The activity of the supramammillary nucleus, median raphe nucleus, and nucleus reuniens may influence the hippocampal EEG, particularly theta, and hence hippocampal mnemonic processing, by means of the pathways described in this dissertation.